Restitution analysis of alternans using dynamic pacing and its comparison with S1S2 restitution in heptanol-treated, hypokalaemic Langendorff-perfused mouse hearts
Bibliographic record
Abstract
Action potential duration (APD) and conduction velocity restitution explain the dependence of these parameters on the previous diastolic interval (DI). It is considered to be an adaptive mechanism for preserving diastole at fast heart rates. Hypokalaemia is known to induce ventricular arrhythmias that could be prevented by heptanol, the gap junction uncoupler, mediated through increases in ventricular refractory period (VERP) without alterations in APDs. The present study investigated alternans and restitution properties during normokalaemia, hypokalaemia alone or hypokalaemia with heptanol (0.1 mM) in Langendorff-perfused mouse hearts using a dynamic pacing protocol. APD90 alternans were elicited in the epicardium and endocardium during normokalaemia. Hypokalaemia increased the amplitudes of epicardial APD90 alternans when basic cycle lengths (BCLs) were ≤65 msec, which was associated with increases in maximum APD90 restitution gradients, critical DIs and APD90 heterogeneity. Heptanol (0.1 mM) did not exacerbate or reduce the APD90 alternans or alter these restitution parameters further. By contrast, endocardial APD90 alternans did not show increases in amplitudes during hypokalaemia at short BCLs studied, and restitution parameters were also unchanged. This was true whether in the presence or absence of 0.1 mM heptanol. The study demonstrates that anti‑arrhythmic effects of heptanol exerted during hypokalaemia occurred despite exacerbation of APD90 alternans. This would suggest that even in the presence of arrhythmogenic APD90 alternans, arrhythmias could still be prevented by influencing VERP alone. Restitution data obtained here by dynamic pacing were compared to previous data from S1S2 pacing.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".